Flash chromatography cartridge

ABSTRACT

A low pressure liquid chromatographic cartridge is provided having a tubular polymer container adapted to receive a chromatographic packing material. The container has an outlet port located at a downstream end of the container and container threads formed on an upstream end of the container. A polymer cap having cap threads located on the cap threadingly engage the container threads. An inlet port is located on an upstream end of the cap. A flange depends from the cap and mates with the lip of the container to form a fluid tight seal between the polymer cap and container suitable for use in low pressure liquid chromatography. A locking tab on a skirt of the cap engages a recess on the container when the seal engages the cap and container to lock the cap in position relative to the container. Alternatively, continuous screw threads on the cap and container may hold the parts together.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 10/842,288 filed May 10, 2004, the entire contents of which arehereby incorporated by reference.

BACKGROUND OF THE INVENTION

This invention relates to method and apparatus involving cartridges foruse in flash chromatography and low pressure liquid chromatographyequipment.

Chromatographic analysis passes fluids through columns containingspecially treated sorbent which allows the chemicals in the fluid to beeluted at different times and thus form separated peaks on achromatogram. In order to prepare or clean up the fluid being analyzedthe fluid is often passed through a sorbent under pressure. Further, forlow pressure liquid chromatography (LPLC) or flash chromatography thefluid may be passed through a sorbent at a pressure of 20-100 psi. Thisoperating pressure is sufficiently high that these cartridges, whichhave relative large diameter bodies leak at the seams. Threadedconnections are thus not used to form the body when the body is made ofpolymers. Thus, these cartridges are traditionally made of plastic andhave sonically welded ends. But even that welded construction will leakif there are defects in the welds. That welded construction and theaccompanying manufacturing and material costs cause in undesirably highcosts, especially as the cartridges must be either discarded, or mustunder go extensive and thorough cleaning after a single use, or at mostafter a few uses with similar fluids. There is thus a need for a lowcost, disposable cartridge.

Further, the welded construction requires the chromatographic packingmaterial be placed in the cartridge before it is welded, or it requirescareful packing of the column under pressure, both of which limit theusefulness of the cartridge and increase its cost.

Recently one company has introduced a disposable cartridge made ofmolded polypropylene having an end fitting that uses openings in anumber of cantilever members to engage detent members which fit into theopenings to create an interference fit to snap-lock the end fitting ontothe cartridge. This is described in U.S. Pat. No. 6,565,745. But thisinterference fit is created at the factory and again creates a cartridgethat does not allow the user to easily vary the contents of thecartridge. There is thus a need for a cartridge that allows a user toeasily vary the contents.

Secondary cartridges are sometimes tied into the system for use, butthese secondary cartridges are limited in size to 70 ml (or between20-25 g of material). These secondary cartridges lie with tubing 1 to 2feet away from the sample. The use of secondary cartridges increases theamount of run time and expensive solvent, due to elution of the sample.It causes dilution of sample because the cartridge is 1 to 2 feet awayfrom the sample. The tubing and secondary cartridge also allows theaddition of air which may or may not affect the chemical composition orperformance. Also secondary cartridges have a capacity limit of 20-25 gwhich does need meet the needs of all users since at times up to 60 g isneeded to be loaded. This forces an end user to separate the chemicalsinto several separate cartridges. The secondary cartridge is also anadditional expense, and requires additional time for loading.

There is thus a need for a cartridge that can be sealed to functionunder LPLC pressures but which allows the user to access the inside ofthe cartridge before it is sealed.

Moreover, welded cartridges are limited by being pressure rated to onlyabout 45 psi, due to leaking and instability at higher pressures. Thispressure limits the end user, because high pressures are desirable forseparating chemical compositions that are thick and viscous. Withoutthese higher pressures these thick, viscous chemicals can not bedistinguished. There is thus also a need for a larger capacity cartridgethat can be used at higher pressures, especially for viscous fluids.

In LPLC the fluid sample is sometimes prepared by passing it through oneor more cartridges of different material, each of which has a differentsorbent to clean the fluid of particular undesirable materials orchemicals. Because the fluid sample can vary, a wide variety ofcartridges with different sorbents sealed in the cartridges must bemaintained. Further, the removal and reconnection of these variouscartridges is cumbersome and time consuming, and the cost of eachcartridge is expensive. There is thus a need for a way to reduce thecomplexity and cost of using different sorbents.

Sometimes a Y fitting is used to inject one or more fluids into the LPLCcartridge. The connection and use of these Y fittings is cumbersome.Further, the fitting must be either discarded or cleaned after each use.There is thus a need for a better and less expensive way to introducefluid or materials into the cartridge.

SUMMARY

A low pressure liquid chromatographic cartridge is provided having atubular polymer container adapted to receive a chromatographic packingmaterial. The container has an outlet port located at a downstream endof the container and configured for connecting to chromatographicequipment during use of the cartridge. Container threads are formed onan upstream end of the container. A polymer cap has cap threads locatedon the cap to threadingly engage the container threads. The cap also hasan inlet port located on an upstream end of the container. The port isconfigured for connecting to chromatographic equipment during use of thecartridge. A resilient fluid tight seal is interposed between the capand container suitable for use in low pressure liquid chromatography. Alocking tab is provided on a skirt of the cap and is located andconfigured to engage a recess on the container when the seal engages thecap and container. The locking tab locks the cap in position relative tothe container.

In further variations the seal comprises a resilient ring extending froma top of the cap with the seal being located and sized to engage a lipof the container. Preferably a fluid dispenser is interposed between thecontainer and the cap. The dispenser has a plurality of fluid outletslocated across a substantial portion of a cross-section of the containerto dispense fluid from the inlet of the cap over the cross-section. Thefluid dispenser preferably takes the form of a dish having a pluralityof holes extending through the dish, so as to place the inlet and theoutlet in fluid communication. Moreover, the dish preferably, butoptionally has a rim placed between the cap and the container. Infurther embodiments the locking tab extends parallel to a longitudinalaxis of the container and extends from a distal end of a skirt of thecap. Further, the inlet can take the form of a tube threadingly engagingone of the cap or container, with the tube having a threaded exteriordistal end located on an exterior of the engaged one of the cap orcontainer. Advantageously the seal and lip abut at an inclined anglewith the seal extending inward toward a longitudinal axis of thecontainer and cap. Moreover, the seal preferably joins the top of thecap at a corner which encircles a longitudinal axis of the container.Still further, the fluid dispenser has a periphery located in thatcorner. Preferably chromatographic packing material is placed in thecartridge by the user before the cap is locked onto the container.Preferably, but optionally, the material to be analyzed is also placedin the cartridge by the user before the cap is locked onto thecontainer. This allows the user to custom select and place any of aplurality of different chromatographic packing materials in thecontainer.

In a further embodiment there is provided a low pressure liquidchromatography cartridge having a tubular container adapted to receive achromatographic packing material. The container has an outlet portlocated at a downstream end of the container and configured for use withchromatographic equipment during use of the cartridge. The containeralso has container threads formed on an upstream end of the container. Acap is provided with an inlet port located on an upstream end of thecap, with port being configured for use with chromatographic equipmentduring use of the cartridge. The cap also has cap threads located on thecap to threadingly engage the container threads. Locking means on thecontainer and cap prevent manual removal of the cap. Resilient sealingmeans are provided for sealing the cap to the container when a userplaces the cap on the container and engages the locking means.

In still further variations, the cartridge has means for distributingfluid from the inlet port over a cross-section area of the containerduring use of the cartridge. Moreover, chromatographic packing materialand materials to be analyzed can be placed in the container by the userof the cartridge before the locking means are locked.

There is also provided a method for a user to perform low pressureliquid chromatography. The method includes placing at least onechromatographic packing material in a tubular container which has anoutlet port located at a downstream end of the container. The outlet isagain configured for use with chromatographic equipment. Containerthreads are formed on an upstream end of the container. The methodincludes threadingly engaging threads on a cap with the containerthreads. The cap is also provided with an inlet port on an upstream endof the cap. The method further includes sealing the cap to the containerby tightening the threads and engaging a seal between the cap and thecontainer. The seal provides a fluid tight seal below about 100 psisuitable for LPLC use.

In further variations the method includes locking the cap to thecontainer. A still further variation includes connecting the inlet to asource of fluid for chromatographic analysis; and distributing the fluidfrom the inlet over a cross-section area of the container. Moreover,distributing step preferably, but optionally includes collecting thefluid in a fluid dispenser having a wall with a plurality of holesspread across the cross-section and passing the fluid through thoseholes. Inclining the surface with the holes toward a centrallongitudinal axis of the fluid dispenser which also passes through thefluid dispenser is also a preferred variation. In a still furthervariation the distributing step is performed by a fluid dispenser with aperiphery that is interposed between the cap and the container.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and advantages of the invention will be betterunderstood by reference to the following drawings in which like numbersrefer to like parts throughout, and in which:

FIG. 1 is a perspective view of a first embodiment of a cartridge with ascrew cap;

FIG. 2 is a partial sectional view of the juncture of the cap andcartridge of FIG. 1;

FIG. 3 is a schematic view of the cartridge of FIG. 1 connected tochromatographic equipment;

FIGS. 4 a-b are top and side views, respectively, of the fluid dispensershown in FIG. 1;

FIG. 5 is a partial sectional view of a further embodiment of inlet andoutlet fittings for use with the cartridge of FIG. 1;

FIG. 6 is a plan view showing a further embodiment of a container andlocking mechanism;

FIG. 7 is a partial sectional view of a further embodiment of theconnection of the cap and the container of FIG. 1;

FIG. 8 is a further embodiment of a fluid dispenser;

FIG. 9 is a section of the fluid dispenser of FIG. 8 taken along section9-9 of FIG. 8;

FIG. 10 is a front perspective view of a further embodiment of a cap;

FIG. 11 is a rear perspective view of the cap of FIG. 10;

FIG. 12 is a top plan view of the cap of FIG. 10;

FIG. 13 is a sectional view taken along section 13-13 of FIG. 12;

FIG. 14 is a cross-sectional view of a further embodiment of a containerfor use with the cap of FIG. 10;

FIG. 15 is a partial sectional view taken along circular section 15-15of FIG. 14;

FIG. 16 is a sectional view of a further embodiment of a cap taken alongsection 16-16 of FIG. 19;

FIG. 17 is a sectional view of the cap of FIG. 16, taken along section17-17 of FIG. 19;

FIG. 18 is a circular sectional view taken along section 18-18 of FIG.16; and

FIG. 19 is a top plan view of the further embodiment of the cap of FIG.16.

DETAILED DESCRIPTION

Referring to FIGS. 1-2 and 7, a cartridge is provided comprising tubularcontainer 20 suitable for flash chromatography. The container has a cap28 with inlet and outlet ports 24, and 30, respectively. The container20 has an open end 22 at and upstream or proximal end, and an outletport 24 at a downstream or distal end. A fluid dispenser 26 is placed inor upstream of the open end 22 and a cap 28 is fastened over the openend 22 and fluid dispenser. An inlet port 30 is provided on the cap 28.A locking mechanism 32 is placed on one or both of the container 20 andcap 28 to hold the cap to the container. A seal 48 between the cap 28and container 20 is held in fluid tight compression by mating threads32, 34 and the locking mechanism 32.

In use, the inlet 30 is placed in fluid communication with a source offluid to be processed in a low pressure liquid chromatography (LPLC) orflash chromatography process. Processing or filtering media is placed inthe container 20. The sample fluid to be tested is passed through themedia in the container, and the resulting fluid is removed from theoutlet port 24 for further processing or other treatment or analysis.Preferably, but optionally, the outlet port 24 is placed in fluidcommunication with the LPLC equipment or other chromatographic equipmentfor the processing or treatment. Advantageously the downstream or distalend of the container 20 is slightly curved or domed or inclined so thefluid being processed is funneled toward the outlet 24.

In more detail, the locking mechanism 32 can advantageously, butoptionally take the form of mating threads on the container 20 and thecap 28. FIG. 1 shows external threads 34 on the container mating withinternal threads 36 on a skirt 38 of the cap 28. But the containerthreads 24 could be internal threads and the cap threads 36 could beexternal threads. The threads can 34, 36 be single lead, or multiplelead. The threads 34, 36 can be continuous or segmented.

Preferably, but optionally, a lip or flange 40 extends outward aroundthe outer circumference of the container 20 adjacent the trailing end ofthe threads. Preferably, one or more gaps or spaces or recesses 41 areformed in the flange 40. As used herein, the leading end of the threadsrefers to the ends that first engage the mating threads, and thetrailing end refers to the last to engage end of the threads. Theoutward direction means away from the longitudinal axis 42 of thecontainer 20.

Referring to FIG. 2, the polymer cap 28 is sealed to the polymercontainer 20 sufficiently to allow flash chromatography up to about 100psi. A lip 44 is formed on the distal edge of the skirt 38 of the cap 28so the lip 38 abuts the flange 40 on the container to limit thetightening of the cap on the container 20, and to help seal the cap tothe container. A locking tab 39 extends from the skirt 28 along thedirection of axis 42. The locking tab 39 is sized and shaped to fit intoone of the recesses 41 on the flange 40. Thus, when the cap 28 isthreaded onto the container 20 by threads 34, 36, the tabs 39 advanceaxially along axis 42 and fit into the recesses 41 to lock the cap fromfurther rotation, and to lock the cap from unscrewing and theaccompanying leaking. The tabs could be located on the container and therecesses on the cap.

Advantageously the locking tabs 39 are configured so the shape matchesthat of the flange 40, making it difficult to manually grab the tabs 39and manipulate them to unscrew the cap 28. Advantageously, butoptionally, the distal or downstream edge of the locking tab 39 taperstoward the axis 42 and that helps remove defined edges of sufficientsize that the edge can be manually grabbed, and that helps avoidunlocking the cap. The locking tabs 39 thus provide means for preventingmanual removal of the cap.

A shaped lip 46 is also preferably, but optionally placed around theopening 22 on the proximal or upstream end of the container 20. Theshaped lip 46 is shown as inclined outward at an angle of about 30° froma line parallel to axis 42. The container lip 46 abuts a sealing surface48 on the cap 28 to provide a fluid tight seal. Different angles and lipshapes could be used, especially if different types of seals are used.

The cap sealing surface 48 is shown as comprising an annular sealdepending from the inside of the cap 28. The sealing surface 48 is shownas connected to a top wall 50 adjacent the juncture of the top wall 50with the side walls or skirt 38 of the cap 28. The top wall 50 ispreferably, but optionally slightly domed or slightly curved outward.The sealing surface 46 is advantageously a thin walled ring, andpreferably, but optionally has a slight conical shape narrowing towardthe downstream end of the cap 28 and inward toward the axis 42. The capsealing surface 48 thus preferably has a larger diameter at the upstreamor proximal end where it fastens to the cap 28, and has a smallerdiameter, open end located downstream and inward of the upper end toform a cone with the smaller end facing downstream.

Preferably, but optionally, the cap sealing surface 48 is integrallymolded with the cap 28, although a two part assembly is also believedsuitable. Referring to FIGS. 1-2, a series of rectangular openingsappear near the juncture of the skirt 38 and the top of the cap 28 andthese openings allow mold slides to pass through the cap to integrallymold the seal 48 with the cap. Referring to FIG. 2, at the peripherywhere the cap sealing surface 48 extends downstream and inward towardaxis 42, a corner is formed and the outer edge of the fluid dispenser 26is placed in this corner.

As the cap 28 is threaded onto the container 20 using threads 34, 36,the downstream side of the cap sealing surface 48 abuts the upstreamside of the cap lip 44 to form a fluid tight seal. The cap lip 44 on thedistal or downstream edge of the cap 28 abuts the flange 40 on thecontainer to prevent over-tightening and preferably, but optionally alsoform a redundant seal. As the cap 28 is threadingly tightened on thecontainer 28 the conical cap sealing surface 48 is resiliently urgedtoward the container lip 46, squeezing and further sealing the peripheryof the fluid dispenser 26 between the seal 48 and the cap 28. The fluiddispenser is thus held between the container and the cap, anddistributes fluid along axis 42 across at least a substantial portion ofa cross section of the container.

Referring to FIGS. 1, 2 and 4, the fluid dispenser 26 has a containingvolume within which the fluid being processed collects and spreads overthe cross-section of the container 20 in order to more evenly distributethe fluid over the material in the container. A plurality of holes 52 inthe downstream surface of the fluid dispersing device allow the fluid toexit the fluid dispenser 26. Various shaped fluid dispensers 26 could beused, including a container with a flat bottom, or inclined bottoms. Asused herein, inclined surfaces include curved surfaces. As the container20 is preferably, but optionally cylindrical in shape, these shapesresult in a cylinder with a flat bottom, or a shallow conical surface ora downwardly curved surface. A flat surface on the dispensing devicerisks some fluid collecting in the device, and is thus not preferred.Various shaped and sized holes and hole patterns could also be used,with the holes 52 being preferably arranged to distribute the fluidbeing processed evenly over the cross-sectional area of the container20. If a curved fluid dispenser 26 is used then the holes 52 mayadvantageously be larger in diameter as the holes get further from thelongitudinal axis.

Still referring to FIGS. 1-2 and 4 the fluid dispenser 26 comprises acircular, domed dish having a plurality of holes 52 extending throughthe dish. The dish shaped fluid dispenser 26 is preferably, butoptionally curved toward the downstream direction so that fluid enteringthe cap 28 through the inlet port 30 collects in the dish and passesthrough the holes 52. One hole is preferably located at the lowermost ormost downstream portion of the surface to avoid fluid collecting in thefluid dispenser 26. Preferably the lowest opening 52 is on thelongitudinal axis 42. A lip or rim of the dispenser is held between thecontainer 20 and the cap 28, and in the preferred embodiment is held bythe lip of the container resiliently urging the seal 48 against the rimof the dispensing device 26 against the top 50 of the cap.

The fluid entering the cap 28 through inlet port 30 enters at pressuresof about 20-100 psi, and preferably about 50 psi, and at a flow rate ofabout 10-100 mL/min, although the pressure and flow rate can vary. Thepressure and flow rate of the fluid entering the cap 28 and collectingon the fluid dispenser 26 is sufficient that the fluid spreads acrossthe upstream surface of the dish shaped fluid dispenser 26 and squirtsthrough the holes 52 like a showerhead to more evenly distribute thefluid over the cross-section of the container.

Referring to FIGS. 1-3, the container 20 is at lest partially filledwith a chromatographic packing material 60 selected to suit the fluidsbeing analyzed and the operating pressures and conditions. This isadvantageously done by the user just before the cap 28 is locked ontothe container 20. Various silica based sorbents are commonly used, andvarious sorbents 60 a, 60 b (FIG. 2) or other chromatographically usefulmaterials can be layered by the user to achieve different effects on thefluid being processed. The level of the chromatographic packing material60 can be varied by the user to leave a predetermined volume inside thecontainer 20, with fluids or other materials being added to fill thatpredetermined volume.

The dish shaped dispensing device 26 is preferably thin, with athickness of about 1/16 inch (16 mm) is believed suitable when the dishis made of polypropylene. The thickness and material will vary with theoperating pressures and fluids being used. A radius of curvature ofabout 1-2 inches for the dish shaped dispensing device is believedsuitable, and 1.5 inch curvature is used in one embodiment, but othercurvatures could be used. The holes 52 are preferably, but optionallyall the same diameter and are equally spaced. A diameter of about 0.03to 0.04 inches (about 7-10 mm) for the holes 52 is believed suitable.The spacing and size of the holes 52 can vary to suit the fluids andpressures being used, and are preferably varied to ensure uniform flowthrough the dispensing device 26 across the entire cross-section of thecontainer. The dispensing device 26 can be made of materials suitablefor the processing of the desired fluid. The fluid dispenser 26 ispreferably made of a polymer, such as polyethylene or polypropylene, andpreferably of high density polypropylene. Other polymers can be used,although are preferably used that are low cost and suitable forinjection molding to form disposable containers and caps. But metaldispensing devices are also believed suitable, such as stainless steel.

Referring to FIGS. 1 and 3, in use a desired amount of filtering mediaor chromatographic packing material 60, such as a silica sorbent, isplaced in the downstream end of the container 20 by the user. Removing apartially secured, and unlocked screw cap 28 allows easy access to placethe chromatographic packing material 60 in the container, to adjust theamount of material in the container, to add a different material orsorbent to the container or to adjust the amount of free volume in thecontainer to receive the sample fluid or material or sorbent. A frit 62can optionally be placed on the upstream and/or downstream end of thechromatographic packing material 60 as desired. The cap 28 and fluiddispenser 26 are then fastened to the container 20 to seal the media 60inside the container 20. The inlet port 24 can then be connected to achromatographic fluid source or fluid pressurizing source 64 and theoutlet 26 connected to chromatographic processing equipment 66 usingtubing 68 which tubing is typically flexible. The cap 28 is preferablynot removable from the container 20 once it is installed by the end userand the locks 29 engage the recesses 41. Thus, any adjustment of thechromatographic packing material 60 or other contents of the container20 is done before the cap 28 is sealingly fastened to the container 28.The fluid to be processed is then passed through the inlet 30, throughthe fluid dispersing device 26, through the contents of the container 20(e.g., through chromatographic packing material 60) and out the outlet24. After use the container 20 and cap 28 can be discarded.

This user access and easy modification of the contents of the cartridgewas not previously possible as the containers were welded shut at thefactory to ensure they didn't leak under the operating pressures. Thereis thus advantageously provided a low cost, disposable cartridge made ofa polymer which has a threaded, sealed cap on the container. The lockingtabs 39 and mating recesses 41 provide locking means on the containerand cap for preventing manual removal of the cap. The locking tab 39forms a member resiliently urged into a recess, and various arrangementsof such resiliently engaging parts, such as various forms of springloaded detents and spring loaded mating members can be devised to formthe locking means, especially given the disclosures herein. The seal 48and lip 46 provide resilient sealing means for sealing the cap to thecontainer when a user places the cap on the container. The sealing meansincludes numerous other seal types, including one or more O ring sealsinterposed between abutting portions of the cap 28 and container. 20

There is also provided a method in which a chromatographic packingmaterial 60 is placed in a container either by the manufacturer, or theuser, but with the cap not being locked to the container, as bypartially threading the cap onto the container but not engaging thelocking tabs 39 with the recesses 41. Alternatively, the cap is notplaced on the container. The user removes the cap 28 and either altersthe prior amount of chromatographic packing material 60, or addschromatographic packing materials of a different type, or adds furthermaterials or chemicals to affect the fluid being processed by the userin the cartridge, or even adds analyte or fluid to be analyzed. The userthen places the cap 28 on the container and seals and locks the cap tothe container 20. The desired processing is then performed using thecartridge and modified sorbent contained in the cartridge. Given theability to remove the cap 28 and access the inside of the container 20immediately before fluid is passed through the container, a variety ofprocess variations can be devised.

The inlet and outlet ports 30, 24, respectively preferably comprisefittings adapted for use in chromatographic applications, and Luerfittings are commonly used. Advantageously the desired fittings at ports24, 30 are integrally molded with the container 20 and cap 28 to form aunitary construction.

Referring to FIG. 5, in a further embodiment the fittings can comprisemetal or plastic tubes 72 having external engaging threads 74 adaptedfor use with chromatographic equipment. A ¼-28 threaded fitting isbelieved suitable for the engaging threads 74. The tubes 72 can have anopposing end with sealing threads 76 configured to sealingly engagemating threads formed at the location of one or more of the ports 24,30. The threaded portion of the cap 28 and container 20 may need to bethickened to provide sufficient threaded engagement. The sealing threads76 preferably form a seal suitable for use up to about 100 psi orhigher. Using slightly different thread dimensions or lead angles on themating threads of the fitting 72 and container or cap can help achievethe desired leak proof seal.

Referring to FIG. 7 a slightly different cap and container are shown inwhich there are continuous threads 34, 36. There is no flange 40 on thecontainer 20, and the lip on the container is only slightly inclinedaway from the longitudinal axis 42. The fluid dispenser 26 is held in acorner formed by a slight inward projection of the cap which projectionextends toward the axis 42. The fluid dispenser 26 can be snapped intoposition in the cap 28, and tightening the cap onto the containerpreferably, but optionally helps further squeeze the periphery of thedispenser 26 between abutting portions of the cap. FIG. 7 shows the top59 with an annular recess 51 which allows the thickness of the top 50 toremain fairly constant which helps molding of the cap 28. Further, therecess 51 adds flexibility to the sealing surface 48 on the cap 50 andthat is believed to enhance the performance of the fluid tight sealwhich must maintain the seal under flash chromatography and LPLCconditions.

Referring to FIGS. 8-9, a further embodiment of the fluid dispenser 26is shown which has a generally a disk shaped support for a plurality ofradially extending flow channels 84 having openings 86 in fluidcommunication with inlet 88. Fluid to be analyzed enters through centralinlet 88 that is advantageously located on the longitudinal axis 42, andflows across the cross-section of container 20 (FIG. 1) through channels86 and then out openings 86 onto the packing material. The openings 86are preferably at the distal end of each channel 86, but could belocated at one or more locations along the length of channel 86. Thisconfiguration is more difficult to mold than the fluid dispenser ofFIG. 1. This embodiment of the fluid dispenser 26 is held between thecap 28 and container 34 as is the prior embodiment of the fluiddispenser. Various ways of holding the fluid dispenser 26 in the desiredposition will be apparent to one skilled in the art given thedisclosures herein, including various clamps, ledges, snap-fits. Thevarious forms of the fluid dispenser 26 comprise means for distributingthe fluid to be analyzed over the packing material and over thecross-section of the container 20.

The threads 24, 36 provide means for fastening the cap 28 to thecontainer 20. But the threads represent one specific form of inclinedmating surfaces, and other means for fastening the cap to the containerinclude the broader use of inclined mating surfaces. Thus, a lug 78 onone of the cap 28 or container 20 can mate with a bayonet mount 80 onthe other of the cap or container to fasten the cap to the container.Placing the recess 41 on a trailing end of an inclined surface on thebayonet could allow the bayonet to also lock the lug into position so asto combine the locking means and the fastening means.

A further embodiment is shown in FIGS. 10-14. The cap 28 has acontinuous skirt 38 that is preferably, but optionally, stiffened withincreased thickness areas, such as by using ribs 90. The ribs 90 arepreferably, but optionally aligned parallel to axis 42. Several groupswith 3-5 ribs in each group are believed suitable. The ribs and anyspaces between the ribs provide for an improved manual griping surfaceto tighten the cap 28. The spacing between groups of ribs is thusadvantageously equal.

The inside of the skirt 38 has threads 34 which mate with threads 36(FIG. 14) on the upstream end of the container 20. The threads arepreferably continuous rather than intermittent or segmented threads. Forcontainers having diameters over about 1 inch (about 2.5 cm) thecontinuous threads provide a more uniform gripping and holding forcebetter suited to resist pressure variations occurring in the container20 during use in flash chromatography. For containers having threads 36about 2 inches (about 5 cm) in diameter or greater the threads arepreferably pipe threads to provide better holding and sealing.

The sealing surface is modified in this alternative embodiment. Thesealing surface is located on an annular sealing flange 48′ having abase on its upstream end that is wider than the downstream, distal end.The sealing flange 48′ has a conical shape, preferably with a flatdistal downstream end. The sealing flange 48′ has two inclined surfaces,one inner surface 48 a faces radially inward toward axis 42, and theother outer face 48 b faces away from axis 42. Inner face 48 a abuts amating face on the container to form a fluid seal as described in moredetail later.

The inner face 48 a is inclined at an angle α of about 7.5° relative toan axis parallel to axis 42. The opposing surface 48 b has a similarangle of inclination, but in the opposing direction, and the angle ofsurface 48 b can vary.

The base of the sealing flange 48′ has a groove 92 encircling theupstream inner periphery of the flange. A slightly raised boss 94 islocated on the downstream edge of the groove 92. The top wall 50 of thecap 28 joins the upstream side of the groove 92 to provide a generallyflat wall joining the upstream wall of groove 92. The juncture with thetop wall could be offset a desired distance, but the tangentialconnection is preferred.

The groove 92 is sized to receive the peripheral edge of the fluiddispensing device 26. The dispensing device is preferably a thin, curvedsurface with holes 52 (FIG. 7). The diameter of groove 92 is sized toreceive the periphery of the dispensing device 26, and is preferablyslightly smaller to slightly compress the dispensing device 26. The boss96 narrows the opening into which the dispensing device 26 is placed, sothe circular periphery of the dispensing device 26 forms a snap-fit withthe groove 92. The flat portion where the upper wall 50 joins the groove90 helps guide the peripheral edge of the fluid dispensing device 26into the groove 90. The inclined inner face 48 a also helps guide thefluid dispensing device toward the groove 90. The tight fit between thecircular dispensing device 26 and the circular groove 92 allows thedispensing device to resist deformation of the cap 28 by abutting thewalls of groove 92 to maintain those walls in a circular configuration.

The annular sealing flange 48′ is offset radially inward from the skirt38 of the cap 28. A shaped annular groove 96 separates the flange 48from the upstream end of the skirt 38. The groove 96 has a conicalcross-section that is narrower at its upstream end and wider at itsdownstream end. The radially inward side of the groove 96 is formed bythe sealing surface 48 b and the radially outward side of the groove 96is formed by inclined surface 98 formed as an inward facing surface onthe inside of the skirt 38, at the upstream end of the skirt. Theinclined surface 98 is inclined relative to axis 42 at an angle β ofabout 10°. The groove 96 has an upstream end 100 which is shaped toconform to the lip of the container 20 defining the opening 22. In theillustrated embodiment the end 100 is flat, located in a planeorthogonal to axis 42.

Referring to FIG. 14, the container lip 46 is shown as flat, and joinstwo inclined sealing surfaces comprising inward facing sealing surface102 a and outward facing sealing surface 102 b. The sealing surfaces 102a, 102 b are inclined toward each other in an upstream direction to forma generally conical cross section having a top surface comprising lip46.

The sealing surfaces are about 0.2 inches (0.5 cm) long measured alongaxis 42. Inward facing sealing surface 102 a is inclined at an angle Δof about 15° relative to axis 42, and sealing surface 102 b is inclinedat an angle θ of about 10° relative to axis 42. Threads 36 extend fromthe downstream end of the surfaces 102 a, 102 b to the outwardlyextending flange 40. Shaped groove 96 is formed to receive the lip 46,with the surface 98 having a length about the same as or slightly longerthan abutting surface 102 b. The threads 36 in the cap 28 preferablystop before inclined sealing surface 98, but could be formed in theinclined surface 98.

The lip 46 defines the upstream opening 22 to the container 20. Thecontainer has a downstream end that is domed to better withstandincreased operating pressures and to accommodate larger diametercontainers 20.

Referring to FIGS. 13-15, the seal between the cap 28 and container 20is described. The shaped groove 96 is configured to receive and sealsboth sides of the container adjacent the lip 46. The inward facingsurface 98 on the skirt 38 of the cap abuts and seals against outwardfacing surface 102 b of the container lip. The outward facing surface 48b of the annular seal 48′ abuts and seals against the inward facingsurface 102 a of the container's lip. The surfaces 102 a, 102 b areinclined at 15° and 10°, respectively, and they abut surfaces 48 b and98 respectively, which are inclined at angles of about 7.5° and 10°,respectively. The abutting surfaces 102 a, 48 b are inclined so there isan angle of about 7.5° of interference. The abutting surfaces 102 b, 98are inclined so there is little or no interference. The interferencefit, abutting surfaces 48 b, 102 a are radially inward of abuttingsurfaces 98, 102 b. The skirt 38 and mating surfaces 102 b, 98 thus forma relatively rigid support to prevent radially outward movement ofinclined surface 48 b, so that surface 102 a is tightly forced againstmating surface 48 b to form a seal.

Advantageously the lip 46 is advanced into shaped groove 96 until thelip 46 abuts the end 100 to form a further sealing surface. Outwardlyextending flange 40 abuts the lip 44 on the cap to preventover-tightening and stripping of the threads 34, 36.

Viewed in cross-section, the lip 46 of the container 20 forms atrapezoidal surface and the shaped channel has a similar shapedtrapezoidal cross-sectional shape in which the outward located inclinedwalls are inclined at about the same angle, while the inward locatedwalls are inclined for an interference, sealing fit. During use thepressure in low pressure liquid chromatography container 20 can reach100 psi or more. The radially outward pressure on inner surface 48 aurges the flange 48′ against the container interposed between the flange48′ and skirt 38 to provide further sealing pressure between theabutting surfaces 48 b and 102 a, and between abutting surfaces 102 band 98.

Further, the circular groove 92 is located downstream of the end 100 ofthe shaped groove 96, and on opposing sides of the annular flange 48′.The circular groove 92 forms a narrower cross-section at the base of theflange 48′ so that the flange tends to flex locally at or by thelocation of the groove. That localized bending allows a greater contactsurface between abutting surfaces 48 b and 102 a. The localized bendingat circular groove 92 also causes the walls forming the groove 92 tomore tightly grip the periphery of the fluid dispensing device 26located in the groove, and that provides greater resistance todeformation of the circular shape of the groove that may be caused byincreased pressure in the low pressure liquid chromatographic container20.

The angles α and Δ can vary, but advantageously create an interferenceon the mating surfaces. Interference angles of 5-15° are believedsuitable. The angle α can be from about 7° to 15°. Larger angles up toabout 30° are believed possible, but are not as suitable. Angles of 6°or less are not desirable because they can leak at higher pressuresand/or with larger diameters of the container 20. The angles β and θ arepreferably the same, and can vary from the 10° angle of the preferredembodiment. Angles from 7-15° are believed suitable for β and θ. Slightinterference angles can be used, but are not preferred. The above anglesand dimensions are believed suitable when the cap 28 and container 20are made of polypropylene, such as PP9074 med polypropylene. Thedimensions can vary with different materials and operating conditionsfor the low pressure liquid chromatographic container 20.

Referring to FIGS. 16-19, a further embodiment is disclosed that isparticularly suited for larger diameter containers 20, or higheroperating pressures, or both. In this embodiment, the skirt 38 isthickened in the radial dimension, and the top wall 50 is alsothickened. The continuous internal threads 34 comprise power threadshaving lower angles of inclination on the leading thread face and aneven lower angle of inclination on the trailing face of the thread. Aflat crest and an increased thickness is typically provided between thethread root and crest. A NPT Thread is preferred. These NPT Threadsrequire more force to unscrew the threads and that prevents loosening ofthe cap under pressure variations that may occur during chromatographicuse. The thickened threads also carry more force along the direction ofaxis 42 so as to accommodate larger forces on the cap 28. The thickenedflange provides radial stiffness and further ensures a slidinginterference fit between surfaces 48 b and 102 a (FIG. 14).

The threads 34 can stop at about the location on axis 42 of the distalend of flange 48′ and the beginning of the shaped recess 96, or thethreads can continue into the shaped recess 96 as is shown. When thethreads 34 extend into the inclined surface 98, the surface becomesintermittent and the seal is not as good. The container 20 will havecorrespondingly shaped external or male NPT Threads 36, but those arenot shown.

Preferably, but optionally, the cap 28 also has a number of externalribs 104 to strengthen the cap. Preferably, but optionally, some of ribs104 extend only over the top wall 50, while others continue along theexterior of the flange 38. The depicted embodiment has two ribs 104 aextending only over the top wall 50, and two ribs extending over the topwall 50 and the flange 38. In addition to strengthening the cap 50, therigs also provide a manual gripping surface.

In the embodiments of FIGS. 10-19, it is believed possible to omit theinclined surfaces 98, 102 b and provide the seal between inclinedsurfaces 102 a and 48 b. The surfaces 48 b and 102 a are generallyaligned, as are the inclined surfaces 98 and 102 a. While the surfacesmay be inclined to form an interference fit as they slide along eachother as the cap is advanced along axis 42 as it is screwed onto thecontainer, the surfaces are aligned sufficiently to abut and form asealing surface.

In the embodiments of FIGS. 10-19, the fluid inlet 30 is integrallymolded with the cap 28. But it could be an inserted fitting as describedherein. Likewise the outlet is shown as integrally molded, but it couldbe an inserted fitting as described herein.

As required, detailed embodiments of the present invention are disclosedherein; however, it is to be understood that the disclosed embodimentsare merely exemplary of the invention, which may be embodied in variousforms. Therefore, specific structural and functional details disclosedherein are not to be interpreted as limiting, but merely as a basis forthe claims and as a representative basis for teaching one skilled in theart to variously employ the present invention in virtually anyappropriately detailed structure.

The above description is given by way of example, and not limitation.Given the above disclosure, one skilled in the art could devisevariations that are within the scope and spirit of the invention,including various ways of sealing the cap to the container and variousprocess steps that alter the material in the container through which thefluid being analyzed is passed. Further, the various features of thisinvention can be used alone, or in varying combinations with each otherand are not intended to be limited to the specific combination describedherein. Thus, the invention is not to be limited by the illustratedembodiments but is to be defined by the following claims when read inthe broadest reasonable manner to preserve the validity of the claims.

1-22. (canceled)
 23. A method for a user to perform low pressure liquidchromatography, comprising: placing at least one of a material to beanalyzed or a chromatographic packing material in a tubular polymercontainer having an outlet port located at a downstream end of thecontainer and configured for use with chromatographic equipment, thecontainer having container threads formed on an upstream end of thecontainer; threadingly engaging threads on a polymer cap with thecontainer threads, the cap having an inlet port on an upstream end ofthe cap; and sealing the cap to the container by tightening the threadsand engaging a seal between the cap and the container, the sealproviding a fluid tight seal below about 100 psi suitable for LPLC use.24. The method of claim 23, further comprising locking the cap to thecontainer.
 25. The method of claim 23, wherein the user changes one ofthe sorbent type, sorbent volume, empty volume of the container, or addsa fluid before sealing the cap to the container.
 26. The method of claim23, further comprising connecting the inlet to a source of fluid forchromatographic analysis; and distributing the fluid from the inlet overa cross-section area of the container.
 27. The method of claim 26,wherein the distributing step comprises collecting the fluid in a fluiddispenser having a wall with a plurality of holes spread across thecross-section and passing the fluid through those holes.
 28. The methodof claim 27, further comprising inclining the surface with the holestoward a central longitudinal axis of the fluid dispenser which alsopasses through the fluid dispenser.
 29. The method of claim 26, whereinthe distributing step is performed by a fluid dispenser with a peripherythat is interposed between the cap and the container.
 30. The method ofclaim 23, wherein the placing step comprises placing a material to beanalyzed in the container.
 31. The method of claim 23, wherein theplacing step comprises placing a chromatographic packing material in thecontainer or removing chromatographic packing material from thecontainer.
 32. The method of claim 23, wherein the sealing stepcomprises abutting first and second oppositely inclined surfaces on thecap with first and second oppositely inclined surfaces on opposing sidesof a lip of the container, the abutting surfaces being generallyaligned.